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RNAi pathway is functional in peripheral nerve axons.

Alexander K Murashov1, Vishnu Chintalgattu, Rustem R Islamov

  • 1Department of Physiology, Brody School of Medicine, East Carolina University, 600 Moye Blvd., Greenville, NC 27834, USA. murashoval@ecu.edu

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|January 9, 2007
PubMed
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Axonal protein synthesis is regulated by RNA interference (RNAi) in peripheral nerves. This study shows RNAi components are present in axons and can reduce protein levels, suggesting local control of translation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Axonal translation, or protein synthesis in axons, occurs distantly from neuronal cell bodies.
  • The regulatory mechanisms governing axonal protein synthesis remain largely unknown.
  • RNA interference (RNAi) is a conserved biological process for gene silencing.

Purpose of the Study:

  • To investigate the role of RNA interference (RNAi) in regulating local protein synthesis within axons.
  • To determine if RNAi machinery is present and functional in peripheral mammalian axons.

Main Methods:

  • Detection of RNA-induced silencing complex (RISC) components (Argonaute2, fragile X mental retardation protein, p100, Gemin3) in the sciatic nerve.
  • Application of short-interfering RNAs targeting beta-tubulin III mRNA to the sciatic nerve.

Related Experiment Videos

  • Quantification of beta-tubulin III mRNA and protein levels.
  • Assessment of retrograde labeling in lumbar motor neurons.

    • Main Results:

    • Sciatic nerve axons contain key components of the RNA-induced silencing complex (RISC).
    • Introduction of short-interfering RNAs against beta-tubulin III reduced both mRNA and protein levels in axons.
    • This led to a significant decrease in retrograde labeling of motor neurons, indicating functional impact.
    • RNAi activity in axons was independent of the neuronal cell body and Schwann cells.

    Conclusions:

    • RNA interference (RNAi) is functional in peripheral mammalian axons.
    • Local protein synthesis in axons can be regulated by RNAi.
    • This provides a novel mechanism for the local control of axonal translation.